ABSTRACT: Antibody response to porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) infection, measured as sample-to-positive (S/P) ratio, has been proposed as an indicator trait for improved reproductive performance during a PRRS outbreak in Landrace sows. However, this result has not yet been validated in Landrace sows or evaluated in terminal sire lines. The main objectives of this work were to validate the use of S/P ratio as an indicator trait to select pigs during a PRRS outbreak and to explore the genetic basis of antibody response to PRRSV. Farrowing data included 2,546 and 2,522 litters from 894 Duroc and 813 Landrace sows, respectively, split into pre-PRRS, PRRS, and post-PRRS phases. Blood samples were taken from 1,231 purebred sows (541 Landrace and 690 Duroc) following a PRRS outbreak for subsequent PRRSV ELISA analysis for S/P ratio measurement. All animals had high-density genotype data available (29,799 single nucleotide polymorphisms; SNPs). Genetic parameters and genome-wide association studies (GWAS) for S/P ratio were performed for each breed separately. Heritability estimates (± standard error) of S/P ratio during the PRRS outbreak were moderate, with 0.35 ± 0.08 for Duroc and 0.34 ± 0.09 for Landrace. During the PRRS outbreak, favorable genetic correlations of S/P ratio with the number of piglets born alive (0.61 ± 0.34), number of piglets born dead (-0.33 ± 0.32), and number of stillborn piglets (-0.27 ± 0.31) were observed for Landrace sows. For Duroc, the GWAS identified a major quantitative trait locus (QTL) on chromosome (Chr) 7 (24-15 megabases; Mb) explaining 15% of the total genetic variance accounted for by markers (TGVM), and another one on Chr 8 (25 Mb) explaining 2.4% of TGVM. For Landrace, QTL on Chr 7 (24-25 Mb) and Chr 7 (108-109 Mb), explaining 31% and 2.2% of TGVM, respectively, were identified. Some of the SNPs identified in these regions for S/P ratio were associated with reproductive performance but not during the PRRS outbreak. Genomic prediction accuracies for S/P ratio were moderate to high for the within-breed analysis. For the between-breed analysis, these were overall low. These results further support the use of S/P ratio as an indicator trait for improved reproductive performance during a PRRS outbreak in Landrace sows.